Adolescent-onset of cocaine use is associated with heightened stress-induced reinstatement of cocaine seeking.
Adolescent-onset of cocaine use is associated with heightened stress-induced reinstatement of cocaine seeking.
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DOI：
10.1111/adb.12284
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发表时间：
2016-05
影响因子：
3.4
通讯作者：
Marinelli M
中科院分区：
文献类型：
--
作者：
Wong WC;Marinelli M
青春期大鼠比成年大鼠更容易吸食可卡因，对较低剂量的毒品更敏感，并且更努力地工作。目前尚不清楚青少年开始使用可卡因是否会对成年后的复发风险产生长期影响。因此，我们测试了在青春期自我服用可卡因是否会影响在长时间不吸毒后，因压力导致的可卡因寻求和服用的恢复。青少年大鼠（~P42）或成年大鼠（P88）自行给药可卡因（0.6或1.2 mg/kg/次）7或10天。然后，他们经历了一段较长时间的禁药期（21-40天），之后，他们接受了由应激激素皮质酮、药理学应激源育亨宾或电击引起的可卡因寻求恢复（即在没有可卡因的情况下做出反应）的测试。研究采用单次灭绝（会话内灭绝/恢复）或在恢复之前重复灭绝（会话间灭绝/恢复）。最后，在另一组单独的实验中，大鼠经历了一段较长时间的无药期（~40天），然后被允许再次自我服用可卡因，使用渐进比例程序来评估可卡因的强化效果。青春期开始使用可卡因的大鼠比成年开始使用可卡因的大鼠表现出更大的压力诱导的可卡因寻求恢复。这是在不同条件下观察到的，为这些结果提供了外部有效性。在渐进比率试验中，各组在药物服用方面没有差异。我们的研究表明，在青少年时期吸食可卡因会使受试者对压力对药物寻求的后续影响特别敏感。这种增加的复吸倾向使青少年开始吸毒的人有更高的复发风险。
Adolescent rats take cocaine more readily than adults, are more sensitive to lower doses of the drug, and work harder for it. It remains unknown if adolescent-onset of cocaine use has long-term consequences on adult relapse liability. Therefore, we tested if self-administering cocaine during adolescence impacts subsequent stress-induced reinstatement to cocaine seeking and taking, after a prolonged drug-free period. Adolescent (~P42) or adult (P88) rats self-administered cocaine (0.6 or 1.2 mg/kg/infusion) for 7 or 10 days. Then, they underwent a prolonged drug-free period (21–40 days), after which they were tested for reinstatement of cocaine-seeking (i.e. responding in the absence of cocaine) induced by the stress hormone corticosterone, the pharmacological stressor yohimbine, or electric footshock. Studies employed either single extinction session (within-session extinction/reinstatement) or repeated extinction prior to reinstatement (between-session extinction/reinstatement). Finally, in a separate set of experiments, rats underwent a prolonged drug-free period (~40 days) and were then allowed to self-administer cocaine again, using progressive-ratio procedures that appraise the reinforcing efficacy of cocaine. Rats with adolescent-onset of cocaine use showed greater stress-induced reinstatement of cocaine seeking than rats with adult-onset of cocaine use. This was observed across conditions, providing external validity to these results. Groups did not differ on drug taking in progressive-ratio tests. Our studies indicate that experiencing cocaine during adolescence renders subjects particularly responsive to the subsequent effects of stress on drug seeking. This heightened propensity for reinstatement puts adolescent-onset drug users at heightened risk for relapse.